Research:

We use budding yeast to look for general principles that underlie the
function and evolution of cells, as revealed by studying the transmission
of genetic information during cell division, mating, and how cells evolve
in response to selective pressure. We try to make quantitative measurements
that discriminate amongst different classes of models and members of the
lab come from both biology and physics backgrounds. In general, we are
more interested in using genetic and physiological perturbations to understand
the "rules of the game" than understand the chemical functions
of individual proteins.

How does mitosis segregate a cell's chromosomes into two identical sets before
cell division? This question has fascinated biologists for over a century
and is directly relevant to cancer and other important medical problems.
We study two aspects of chromosome behavior: how chromosomes attach to
the chromosome segregation machinery (the spindle) in mitosis and meiosis,
and the spindle checkpoint, the control circuit that cells use to make
sure that their chromosomes are properly lined up on the mitotic spindle
before initiating chromosome segregation.

Budding yeast has two mating types and can exist stably as both haploids and
diploids. We use microfluidics, video microscopy, and genetic manipulation
to ask how cells pick a single axis of polarization when they are exposed
to mating pheromones, how this axis is aligned to pheromone gradients,
and how pairs of cells efficiently court and then fuse with each other
in dense mixtures of mating cells. Our results suggest that cells use
the cytoskeleton to integrate signaling from all parts of the cell surface
in way that guarantees a single axis of polarity.

How does selective pressure induce the evolution of new traits and how predictable
is the outcome of such experiments? We study both general and specific
questions. The general questions include attempting to use theory and
experiment to determine how the rate of evolution depends on population
sizes and the beneficial mutation rate, evolving altered mating preferences
(a first step towards speciation), investigating the advantages of mutators,
evolving cooperation, and determining the distribution of beneficial and
deleterious mutations. The more specific projects use the mating pathway
and attempt to create connections to other signaling pathways and turn
the pathway from a rapidly reversible and graded response into a stable
switch that can be thrown by a single exposure to mating pheromone.